期刊
BIOCHEMISTRY
卷 41, 期 22, 页码 7100-7107出版社
AMER CHEMICAL SOC
DOI: 10.1021/bi025902m
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资金
- NCI NIH HHS [R01 CA034590, CA34590, R01 CA034590-18, R01 CA034590-19, CA68485, CA56704, P30 CA068485] Funding Source: Medline
- BLRD VA [IK6 BX005225] Funding Source: Medline
The CXC subfamily of chemokines plays an important role in diverse processes, including inflammation, wound healing, growth regulation, angiogenesis, and tumorigenesis. The CXC chemokine CXCL1, or MGSA/GROalpha, is traditionally considered to be responsible for attracting leukocytes into sites of inflammation. To better understand the molecular mechanisms by which CXCL1 induces CXCR2-mediated chemotaxis, the signal transduction components involved in CXCL1-induced chemotaxis were examined. It is shown here that CXCL1 induces cdc42 and PAKI activation in CXCR2-expressing HEK293 cells. Activation of the cdc42-PAK1 cascade is required for CXCL1-induced chemotaxis but not for CXCL1-induced intracellular Ca2+ mobilization. Moreover, CXCL1 activation of PAKI is independent of ERK1/2 activation, a conclusion based on the observations that the inhibition of MEK-ERK activation by expression of dominant negative ERK or by the MEK inhibitor, PD98059, has no effect on CXCL1-induced PAK1 activation or CXCL1-induced chemotaxis.
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